Clinical trial Recruiting at 4 sites Phase 1 Interventional Ages 18 and up

Cevostamab in relapsed or refractory multiple myeloma

Official title: An Open-Label, Multicenter, Phase Ib Trial Evaluating the Safety, Pharmacokinetics, and Activity of Cevostamab as Monotherapy and Cevostamab Plus Pomalidomide and Dexamethasone or Cevostamab Plus Daratumumab and Dexamethasone in Patients With Relapsed or Refractory Multiple Myeloma

Run by Genentech, Inc. · NCT04910568 · Data updated 2026-11-12

This early-stage trial tests cevostamab alone or with standard therapies to see if it is safe and how it behaves in people with relapsed or refractory multiple myeloma.

Quick facts

PhasePhase 1
Study typeInterventional
Ages18 Years and up
SexAll
Enrollment186 (estimated)
SponsorGenentech, Inc.
Industry-sponsored
Drugs / interventionscevostamab, tocilizumab, daratumumab, CAR T, chimeric antigen receptor, radiation, prednisone
Locations34 sites (Duarte, California and 33 other locations)
StatusRecruiting
StartedJuly 26, 2021
Main results expectedDecember 21, 2028
Study endsDecember 21, 2028
Registry record updatedOctober 20, 2026
Trial IDNCT04910568 on ClinicalTrials.gov

Is this trial a fit for you?

Likely a good fit

Adults with relapsed or refractory multiple myeloma who have measurable disease and adequate organ function, and who have had prior anti-mye therapy with appropriate recovery from prior treatments.

Probably not a fit

Patients with rapidly progressing disease or those not deriving benefit from the study treatments may not experience improvement.

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This is a Phase 1, multicenter, open-label study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of cevostamab as a single agent and in combination with pomalidomide-dexamethasone or daratumumab-dexamethasone in patients with relapsed or refractory multiple myeloma. Participants will receive intravenous infusions and be closely monitored for adverse events and drug behavior in the body. The trial aims to establish a safe dose range and explore preliminary anti-myeloma activity of the regimens. Eligibility requires measurable disease, good performance status, and prior therapy considerations; women and men have contraception or abstinence requirements during and after treatment. Locations include three U.S. cancer centers with Genentech and Roche as sponsors.

Why it matters

Potential benefit: If successful, cevostamab-based regimens could offer a new treatment option for patients with relapsed or refractory multiple myeloma.

How similar studies have gone: Previous studies with similar monoclonal approaches in myeloma have shown signals of activity and acceptable safety in early phases, supporting further exploration.

Who can join: the full rules

Show full inclusion / exclusion criteria
Inclusion Criteria:

* Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
* Life expectancy of at least 12 weeks
* Agreement to provide bone marrow biopsy and aspirate samples
* Resolution of adverse events from prior anti-cancer therapy to Grade \<=1
* Measurable disease
* For women of childbearing potential: agreement to remain abstinent or use contraception, during the treatment period (including treatment interruptions) and for at least 5 months after the last dose of cevostamab and at least 3 months after the last dose of tocilizumab was administered
* For men: agreement to remain abstinent or use a condom, and agreement to refrain from donating sperm, during the treatment period, and for at least 2 months after the last dose of tocilizumab was administered to avoid exposing the embryo and sexual partner Additional Arm A-Specific Inclusion Criteria
* Diagnosis of R/R MM for which no established therapy for MM is appropriate and available, or intolerance to those established therapies Additional Arm B-Specific Inclusion Criteria
* For Cohort B1S: Participants with R/R MM who have received at least two prior lines of treatment, including a proteasome inhibitor (PI) and an immunomodulatory drug (IMiD)
* For Cohort B2S, B1E, B3E: Participants with R/R MM who have received at least one prior line of treatment that included at least two consecutive cycles of treatment, including a PI and an IMiD
* For Cohort B4E: Participants with R/R MM who have received one to four lines of prior therapy that included at least two consecutive cycles of anti-CD38 therapy, lenalidomide and a PI, and either: Prior B-cell maturation antigen- (BCMA)-targeted therapy-directed chimeric antigen receptor T (CAR T) cell therapy or Prior BCMA-antibody-drug conjugate (ADC) therapy
* Agreement to comply with all requirements of the pomalidomide pregnancy prevention program
* For women of childbearing potential: agreement to remain abstinent or use two reliable methods of contraception starting at least 4 weeks prior to, during the treatment period, and for at least 4 weeks after the last dose of pomalidomide was administered
* For men: agreement to remain abstinent or use a condom during the treatment period and for at least 4 weeks after the last dose of pomalidomide, (even if he has undergone a successful vasectomy) and agreement to refrain from donating sperm and blood during this same period Additional Arm C-Specific Inclusion Criteria
* For Cohort C1S: Patients with R/R MM who have received at least two prior lines of treatment including a PI and an IMiD
* For Cohort C2S and additional cohorts: Participants with R/R MM who have received at least 1 prior line of therapy
* For women of childbearing potential: agreement to remain abstinent or use contraceptive methods during the treatment period and for at least 102 days after the last dose of daratumumab was administered
* For men: agreement to remain abstinent or use a condom during the treatment period and for at least 102 days after the last dose of daratumumab was administered to avoid exposing the embryo, and agreement to refrain from donating sperm during this same period

Exclusion Criteria:

* Prior treatment with cevostamab or another agent targeting FcRH5
* Inability to comply with protocol-mandated hospitalization and activities restrictions
* Pregnant or breastfeeding, or intending to become pregnant during the study or within 5 months after the last dose of cevostamab or within 3 months after the last dose of tocilizumab (if applicable).
* Prior use of any monoclonal antibody, radioimmunoconjugate, or antibody-drugconjugate as anti-cancer therapy within 4 weeks before first study treatment, except for the use of non-myeloma therapy
* Prior treatment with systemic immunotherapeutic agents, including, but not limited to, cytokine therapy and anti-CTLA4, anti-PD-1, and antiPD-L1 therapeutic antibodies within 12 weeks or 5 half-lives of the drug, whichever is shorter, before first study treatment
* Prior treatment with CAR T-cell therapy within 12 weeks before first study treatment
* Treatment with radiotherapy within 4 weeks (systemic radiation) or 14 days (focal radiation) prior to first study treatment
* Treatment with any chemotherapeutic agent or other anti-cancer agent (investigational or otherwise) within 4 weeks or 5 half-lives of the drug, whichever is shorter, prior to first study treatment
* Autologous SCT within 100 days prior to first study treatment
* Prior allogeneic stem cell transplant(ation) (SCT)
* Circulating plasma cell count exceeding 500/micro L or 5% of the peripheral blood white cells
* Prior solid organ transplantation
* History of autoimmune disease
* History of confirmed progressive multifocal leukoencephalopathy
* History of severe allergic or anaphylactic reactions to monoclonal antibody therapy
* Known history of amyloidosis
* Lesions in proximity of vital organs that may develop sudden decompensation/deterioration in the setting of a tumor flare
* History of other malignancy within 2 years prior to screening
* Known treatment-related, immune-mediated adverse events associated with prior checkpoint inhibitors
* Current or past history of central nervous system (CNS) disease, such as stroke, epilepsy, CNS vasculitis, neurodegenerative disease, or CNS involvement by MM
* Significant cardiovascular disease
* Symptomatic active pulmonary disease or requiring supplemental oxygen
* Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection
* Known or suspected chronic active Epstein-Barr virus (EBV) infection
* Recent major surgery within 4 weeks prior to first study treatment
* Positive serologic or PCR test results for acute or chronic hepatitis B virus (HBV) infection
* Acute or chronic hepatitis C virus (HCV) infection
* Known history of Grade \>= 3 CRS or immune effector cell-associated neurotoxicity syndrome (ICANS) with prior bispecific therapies
* Known history of hemophagocytic lymphohistiocytosis (HLH) or immune effector cell associated hemophagocytic lymphohistiocytosis like syndrome (IEC HS)
* Active symptomatic coronavirus disease 2019 (COVID-19) infection at study enrollment or requiring treatment with intravenous (IV) antiviral where the last dose of IV antiviral treatment was given within 14 days prior to first study treatment. Patients with active COVID-19 infection must have clinical recovery and two negative antigen tests at least 24 hours apart prior to first study treatment
* Positive and quantifiable EBV polymerase chain reaction (PCR) or Cytomegalovirus (CMV) PCR prior to first study treatment
* Known history of HIV seropositivity
* Administration of a live, attenuated vaccine within 4 weeks before first study treatment or anticipation that such a live attenuated vaccine will be required during the study
* Treatment with systemic immunosuppressive medications, with the exception of corticosteroid treatment \<=10 mg/day prednisone or equivalent, within 2 weeks prior to first study treatment
* History of illicit drug or alcohol abuse within 12 months prior to screening, in the investigator's judgment Additional Arm B-Specific Exclusion Criteria
* Pregnant or breastfeeding, or intending to become pregnant 4 weeks prior to initiation of study treatment, during the study, (including treatment interruptions) or within 4 weeks after the last dose of pomalidomide
* Significant cardiovascular disease (such as, but not limited to, New York Heart Association Class III or IV cardiac disease, myocardial infarction within the last 12 months, uncontrolled arrhythmias, or unstable angina)
* History of erythema multiforme, Grade \>=3 rash, blistering, or severe hypersensitivity to prior treatment with immunomodulatory drugs such as thalidomide, lenalidomide, or pomalidomide
* Inability to tolerate thromboprophylaxis, or contraindication to thromboprophylaxis
* GI disease that might significantly alter absorption of oral drugs Additional Arm C-Specific Exclusion Criteria
* Pregnant or breastfeeding, or intending to become pregnant during the study or within 102 days after the last dose of daratumumab
* Known hypersensitivity to biopharmaceuticals produced in CHO cells or any component of daratumumab formulations
* Known chronic obstructive pulmonary disease (COPD) with a forced expiratory volume in 1 second (FEV1) \<50% of predicted normal
* Known moderate or severe persistent asthma within the past 2 years, or current uncontrolled asthma of any classification

Where it's running

  • Colorado Blood Cancer Institute (CBCI) at Presbyterian/ St. Luke's Medical Center
    Denver, Colorado, United States
    Recruiting
  • The Alfred Hospital
    Melbourne, Victoria, Australia
    Recruiting
  • Sourasky Medical Centre
    Tel Aviv, Israel
    Recruiting
  • University College London Hospitals NHS Foundation Trust
    London, United Kingdom
    Recruiting
  • City of Hope
    Duarte, California, United States
    Active not recruiting
  • City of Hope - Lennar Foundation Cancer Center
    Irvine, California, United States
    Active not recruiting
Show 28 more locations
  • Winship Cancer Institute
    Atlanta, Georgia, United States
    Withdrawn
  • Karmanos Cancer Institute.
    Detroit, Michigan, United States
    Completed
  • Washington University School of Medicine
    St Louis, Missouri, United States
    Active not recruiting
  • Peter MacCallum Cancer Centre
    Melbourne, Victoria, Australia
    Active not recruiting
  • Cross Cancer Institute
    Edmonton, Alberta, Canada
    Active not recruiting
  • Hamilton Health Sciences
    Hamilton, Ontario, Canada
    Active not recruiting
  • University Health Network
    Toronto, Ontario, Canada
    Active not recruiting
  • Fakultni Nemocnice Ostrava
    Ostrava, Czechia
    Active not recruiting
  • I Interni klinika
    Prague, Czechia
    Withdrawn
  • Rigshospitalet
    København Ø, Denmark
    Active not recruiting
  • Hôpital Saint-Louis
    Paris, France
    Withdrawn
  • CHU de Poitiers - La Miletrie
    Poitiers, France
    Active not recruiting
  • CHU Pontchaillou
    Rennes, France
    Withdrawn
  • Rambam Medical Center
    Haifa, Israel
    Active not recruiting
  • Asst Papa Giovanni Xxiii
    Bergamo, Lombardy, Italy
    Active not recruiting
  • A.O. Spedali Civili Di Brescia-P.O. Spedali Civili
    Brescia, Lombardy, Italy
    Completed
  • Nagoya City University Hospital
    Aichi, Japan
    Withdrawn
  • National Hospital Organization Okayama Medical Center
    Okayama, Japan
    Withdrawn
  • The Cancer Institute Hospital of JFCR
    Tokyo, Japan
    Withdrawn
  • Yamagata University Hospital
    Yamagata, Japan
    Active not recruiting
  • Uniwersyteckie Centrum Kliniczne
    Gdansk, Poland
    Withdrawn
  • Pratia Onkologia Katowice
    Katowice, Poland
    Active not recruiting
  • Uniwersytecki Szpital Kliniczny w Poznaniu
    Późna, Poland
    Withdrawn
  • Seoul National University Hospital
    Seoul, South Korea
    Active not recruiting
  • Samsung Medical Center
    Seoul, South Korea
    Active not recruiting
  • Hospital Universitari Vall d'Hebron
    Barcelona, Spain
    Active not recruiting
  • Hospital General Universitario Gregorio Marañon
    Madrid, Spain
    Active not recruiting
  • Royal Marsden Hospital
    Sutton, United Kingdom
    Active not recruiting

Study contacts

Similar studies

Other studies for the same condition or treatment. Recruiting studies are listed first.

How to take part

  1. Review the eligibility criteria above with your treating physician.
  2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
  3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.
Last reviewed 2026-11-14 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.